Self-assembly of peptides and proteins into aggregates with a signature of cross-beta conformation is a hallmark of amyloids. Short peptides have provided important insights in understanding the various interactions that drive self-assembly as well as the molecular architecture of the self-assembled structures. The short amyloidogenic-stretch of beta-amyloid, A beta(16-22) (Ac-KLVFFAE-am), is a good model peptide to study the aspects of beta-amyloid fibril formation. In order to investigate how a turn-supporting sequence could modulate the interaction of the Ac-KLVXZAE-am chains, where X and Z are the aromatic amino acids, Phe, Tyr, or Trp, we investigated the self-assembly of Ac-KLVFFAE-am, Ac-KLVFYAE-am, Ac-KLVYYAE-am, and Ac-KLVWWAE-am separated by turn-inducing dipeptide motifs, Asn-Gly, (D)Pro-Gly, and Aib-(D)Pro. The peptides harboring beta-turn-inducing motifs aggregate rapidly causing large enhancements in thioflavin T (ThT) fluorescence compared to control, beta-turn motif lacking peptides. The morphology of fibrils strongly depends on the type of beta-turn. Ac-KLVFYAE-am repeats separated by Aib-(D)Pro and (D)Pro-Gly have the highest aggregation propensity among all the peptides studied; they caused very large enhancement in ThT fluorescence. Ac-KLVYYAE-am is largely non-amyloidogenic; the (D)Pro-Gly and Aib-(D)Pro connected repeats, however, resulted in distinct fibrils that bind ThT. The study indicates that beta-turn motifs can be exploited to modulate and control the aggregation propensity of peptides and the morphology of aggregates.
